Epstein Barr virus DNA analysis in blood predicts disease progression in a rare case of plasmablastic lymphoma with effusion

Friis, Anna; Åkerlund, Börje; Christensson, Birger; Gyllensten, Katarina; Aleman, Anna; Zou, Jie-Zhi; Ernberg, Ingemar

doi:10.1186/1750-9378-8-28

Cited by 7 publications

(2 citation statements)

References 23 publications

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“…The established cell line, PBL-1, had an immunophenotype typical of plasmablasts, with morphological features that resembled plasmacytic tumours. To the best of our knowledge, there have been two previous reports of the establishment and characterization of cell lines from this distinct tumour 33 , 34 , and one report of a xenograft model of EBV-negative-PBL 35 . A study of two EBV-positive cell lines, SPIBL-II and III, established by Friis et al .…”

Section: Discussionmentioning

confidence: 99%

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Interleukin-6-dependent growth in a newly established plasmablastic lymphoma cell line and its therapeutic targets

Mine

Hishima

Suganuma

et al. 2017

Sci Rep

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Plasmablastic lymphoma (PBL) is a rare, highly aggressive subtype of non-Hodgkin lymphoma with plasma-cell differentiation occurring typically in immune-suppressed patients such as those with AIDS. This study reports the establishment and characterization of a new cell line, PBL-1, derived from a patient with AIDS-associated PBL. Morphological assessment of PBL-1 indicated plasma-cell differentiation with a CD20(−) CD38(+) CD138(+) immunophenotype and IgH/c-myc translocation. The cell line harbours Epstein-Barr virus, but a 52.7-kbp length defect was identified in its genome, resulting in no expression of viral microRNAs encoded in the BamHI-A Rightward Transcript region. Importantly, supplementation of culture medium with >5 ng/mL of interleukin-6 (IL-6) was required for PBL-1 growth. Starvation of IL-6 or addition of tocilizumab, an inhibitory antibody for the IL-6 receptor, induced apoptosis of PBL-1. Transduction of IL-6 into PBL-1 by lentivirus vector induced autologous growth without IL-6 supplementation of culture medium. These data indicate the IL-6 dependency of PBL-1 for proliferation and survival. mTOR inhibitors induced cell death effectively, suggesting mTOR in the IL-6 signalling pathway is a potential therapeutic target for PBL. This established PBL cell line will be a useful tool to further understand the pathophysiology of PBL and aid the future development of PBL treatment.

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Section: Discussionmentioning

confidence: 99%

“…A study of two EBV-positive cell lines, SPIBL-II and III, established by Friis et al . did not report the immunophenotype or culture method used including IL-6-dependency 33 . The SPIBL-II and III cell lines were established from the pleural effusion of an HIV-positive case of plasmablastic lymphoma.…”

Section: Discussionmentioning

confidence: 99%

Interleukin-6-dependent growth in a newly established plasmablastic lymphoma cell line and its therapeutic targets

Mine

Hishima

Suganuma

et al. 2017

Sci Rep

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Dual Threat of Epstein-Barr Virus: an Autopsy Case Report of HIV-Positive Plasmablastic Lymphoma Complicating EBV-Associated Hemophagocytic Lymphohistiocytosis

et al. 2018

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Epstein-Barr virus (EBV) reactivation causes serious diseases in immunocompromised hosts, such as acquired immunodeficiency syndrome (AIDS). We report on a case of plasmablastic lymphoma (PBL) with hemophagocytic lymphohistiocytosis (HLH).A-53-year-old Japanese man was diagnosed with PBL and AIDS. In addition to combined antiretroviral therapy, HyperCVAD (cyclophosphamide, doxorubicin, vincristine, prednisone)/high-dose methotrexate + cytarabine was initiated immediately. Partial remission was attained with chemotherapy. However, the patient developed HLH and died despite intensive therapy. Autopsy findings suggested that PBL was controlled, and immunosuppression appeared to cause fatal infection. The patient showed high titers of EBV viral-capsid antigen (VCA)-IgG (1:2560) on PBL diagnosis and high EBV-DNA levels throughout the clinical course. Moreover, EBV-DNA was detected in the fraction of CD8-positive cells, which strongly supports the pathogenesis of EBV-associated HLH.Our report highlights the importance of EBV control in patients with EBV-positive AIDS lymphoma. EBV not only behaves as the etiologic pathogen of PBL but also can be a trigger of HLH, the fatal complication. Careful follow-up of the EBV status should be performed, and if needed, preemptive anti-EBV therapy should also be considered to prevent EBV-associated complications such as HLH.

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Clinical and pathological aspects of human immunodeficiency virus-associated plasmablastic lymphoma: analysis of 24 cases

et al. 2016

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Plasmablastic lymphoma (PBL) is a rare AIDS-related malignancy with a poor prognosis. Little is known about this entity, and no standard treatment regimen has been defined. To establish an adequate treatment strategy, we investigated 24 cases of PBL arising in human immunodeficiency virus-positive individuals. Most of the patients were in the AIDS stage, with a median CD4 count of 67.5/µL. Lymph nodes (58 %), gastrointestinal tract (42 %), bone marrow (39 %), oral cavity (38 %), and CNS (18 %) were the most commonly involved sites. Histology findings for the following were positive at varying rates, as follows: CD10 (56 %); CD30 (39 %); CD38 (87 %); MUM-1 (91 %); CD138 (79 %); EBER (91 %); and LMP-1 (18 %). There was a marked increase in patients in 2011-12, and the cases found in that period appeared to be more aggressive, showing a higher rate of advanced-stage PBL. Fourteen cases were treated with CHOP, while the others were treated with more intensive regimens, including bortezomib and hematopoietic stem cell transplantation. The overall median survival time was 15 months. A CD4 count of >100/µL at diagnosis and attaining complete remission in the first-line chemotherapy were associated with better outcomes (P = 0.027 and 0.0016, respectively). Host immune status and chemosensitivity are associated with improved prognosis in PBL.

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Epstein Barr virus DNA analysis in blood predicts disease progression in a rare case of plasmablastic lymphoma with effusion

Cited by 7 publications

References 23 publications

Interleukin-6-dependent growth in a newly established plasmablastic lymphoma cell line and its therapeutic targets

Interleukin-6-dependent growth in a newly established plasmablastic lymphoma cell line and its therapeutic targets

Dual Threat of Epstein-Barr Virus: an Autopsy Case Report of HIV-Positive Plasmablastic Lymphoma Complicating EBV-Associated Hemophagocytic Lymphohistiocytosis

Clinical and pathological aspects of human immunodeficiency virus-associated plasmablastic lymphoma: analysis of 24 cases

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